Risk and Benefit for Targeted Therapy Agents in Pediatric Phase II Trials in Oncology: A Systematic Review with a Meta-Analysis

Abstract

Background For research with human participants to be ethical, risk must be in a favorable balance with potential benefits. Little is known about the risk/benefit ratio for pediatric cancer phase II trials testing targeted therapies. Objective Our aim was to conduct a systematic review of preliminary efficacy and safety profiles of phase II targeted therapy clinical trials in pediatric oncology. Methods Our protocol was prospectively registered in PROSPERO (CRD42020146491). We searched EMBASE and Pub-Med for phase II pediatric cancer trials testing targeted agents. We included solid and hematological malignancy studies published between 1 January, 2015 and 27 February, 2020. We measured risk using drug-related grade 3 or higher adverse events, and benefit by response rates. When possible, data were meta-analyzed. All statistical tests were two-sided. Results We identified 34 clinical trials (1202 patients) that met our eligibility criteria. The pooled overall response rate was 24.4% (95% confidence interval [CI] 14.5-34.2) and was lower in solid tumors, 6.4% (95% CI 3.2-9.6), compared with hematological malignancies, 55.1% (95% CI 35.9-74.3); p < 0.001. The overall fatal drug-related (grade 5) adverse event rate was 1.6% (95% CI 0.6-2.5), and the average drug-related grade 3/4 adverse event rate per person was 0.66 (95% CI 0.55-0.78). Conclusions We provide an estimate for the risks and benefits of participation in pediatric phase II cancer trials. These data may be used as an empirical basis for informed communication about benefits and burdens in pediatric oncology research.

Clinical impact of molecular genetic testing in pediatric oncology

“…Эффективность применения ТТ в онкопедиатрии оценивается с использованием различных дизайнов клинических исследований, тем не менее на сегодняшний день остается большим вопросом, какая именно категория пациентов в наибольшей степени будет иметь успех при ее назначении [5,34,[37][38][39][40]. В систематическом обзоре J. Lee et al наглядно продемонстрирована частота достижения объективного ответа у пациентов с онкологическими заболеваниями в случаях применения ТТ на основании проведенной молекулярно-генетической диагностики.…”

Proteomics and personalized patient-derived xenograft models identify treatment opportunities for a progressive malignancy within a clinically actionable timeframe and change care

“…Utilizing genomic strategies and clinical data, precision medicine strives for more targeted and less toxic therapies, potentially enhancing outcomes for cancer patients (1, 2). Yet, while actionable genomic or transcriptional level changes are observed in >70% of pediatric and young adult patients with solid tumors, half of patients treated with a targeted therapy show a positive response (3)(4)(5). Genome-driven precision oncology maps the causal alterations, while proteomics provides a quantitative assessment of cellular processes providing complementary insight closer to the disease and therapy response phenotype.…”

Risk and benefit for umbrella trials in oncology: a systematic review and meta-analysis

“…The safety and toxicity rates of anticancer agents in standard phase I-III clinical trials have already been estimated [26][27][28]. The recent analyses were focused on targeted therapies [29,30] which play an important role in precision medicine [31]; the performance of targeted therapies is enhanced when used in combination with cytotoxic drugs [32]. However, the only RCT in precision oncology was negative for survival [33].…”